This application is for competitive renewal of the Program Project grant "Mechanisms of Acute Vascular Reaction to Injury". This is a long- standing program which has explored many of the basic mechanisms underlying vascular pathology, including early studies of molecular mediators of permeability, protein biochemistry of amyloid, mechanisms of action of growth factors in the vessel wall, monoclonality of atherosclerosis, expression of endothelial cell adherence proteins, and identification of smooth muscle subtypes. The renewal projects are focused around cardiovascular developmental biology. The six projects include basic studies of the genes controlling cell lineage in the heart and in smooth muscle cells, molecular signals controlling innervation of vessels, role of the PDGF system in vascular ontogeny, mechanisms of assembly of endothelial cells to form vessels, and the role of these same growth factors and other mechanisms in the formation of neointima as a reaction to vascular injury and possible model for the origins of atherosclerosis. These six projects are served by three cores, including an Embryology core and an Animal core. these cores will help develop new model systems, especially using genetically altered mice, and will provide expertise in their respective areas. An Administrative core will also provide support to the projects. Our ultimate goal is that these studies of basic mechanisms will allow us to understand more general mechanisms of vascular biology that are critical to vascular diseases, including hypertension and atherosclerosis.